GYPB
Encyclopedia
Glycophorin B (gene designation GYPB) also known as sialoglycoprotein delta and SS-active sialoglycoprotein is a protein
which in humans is encoded by the GYPB gene
. GYPB has also recently been designated CD235b (cluster of differentiation
235b).
(GYPA) and B (GYPB; this protein) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinant
s for the MN and Ss blood group
s respectively. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include the Miltenberger (Mi) complex and several isoforms of Stones (Sta); also Dantu, Sat, Henshaw (He or MNS6), Mg and deletion variants Ena, S-s-U- and Mk. Most of these are the result of gene recombinations between GYPA and GYPB.
The gene has 97% sequence homology with the glycophorin A gene from the 5' UTR approximately 1 kilobase upstream from the exon encoding the transmembrane regions to the portion of the coding sequence encoding the first 45 amino acids. There is a signal sequence of 19 amino acid residues. The leader peptide differs by one amino acid and the next 26 amino acids are identical. Amino acids 27-55 of glycophorin A are absent from glycophorin B. This section includes an N-glycosylation site. Only O-glycosylation sites are found on glycoprotein B and these are linked via serine
or threonine
. Residues 80-100 of glycophorin A and 51-71 of glycophorin B are very similar. The intervening residues in contrast differ significantly. The antigenic determinant for the blood group Ss is located at residue 29 where S has a methionine
and s a threonine. This is due to a mutation at nucleotide 143 (C->T). The S antigen is also known as MSN3 and the s antigen as MNS4.
It seems likely that this gene evolved by gene duplication and subsequent mutation of glycophorin A. The transition site from homologous to nonhomologous sequences can be localized within Alu repeat sequences.
The first 40 amino acids of the mature protein are extracellular. The next 22 form a transmembrane segment and the remainder are intra cellular.
The frequencies of these antigens are
Glycophorin B carries the blood group antigens N, Ss and U. Both glycophorin A and B bind the Vicia graminea anti-N lectin. S and s antigens are not affected by treatment with trypsin
or sialidase
but are destroyed or much depressed by treatment with papain
, pronase
or alpha-chymotrypsin.
There are about 40 known variants in the MNS blood group system. These have arisen largely as a result of mutations within the 4 kb region coding for the extracellular domain. These include the antigens Mv, Dantu, Henwshaw (He), Orriss (Or), Miltenberger, Raddon (FR) and Stones (Sta). Chimpanzee
s also have an MN blood antigen system. In chimpanzees M reacts strong but N only weakly.
In individuals who lack both glycophorin A and B the phenotype has been designated Mk.
1-Serine-Threonine-Serine-Glycine
5 while Henshaw has Leucine
1-Serine-Threonine-Threonine-Glutamate5. This antigen is rare in Caucasians but occurs at a frequency of 2.1% in US and UK of African origin. It occurs at the rate of 7.0% in blacks in Natal
and 2.7% in West Africans. At least 3 variants of this antigen have been identified.
Mi-I (Mia), Mi-II(Vw), Mi-VII and Mi-VIII are carried on glycophorin A. Mi-I is due to a mutation at amino acid 28 (threonine to methionine: C->T at nucleotide 83) resulting in a loss of the glycosylation at the asparagine26 residue. Mi-II is due to a mutation at amino acid 28 (threonine to lysine
:C->A at nucleotide 83). Similar to the case of Mi-I this mutation results in a loss of the glycosylation at the asparagine
26 residue. This alteration in glycoslation is detectable by the presence of a new 32kDa glycoprotein stainable with PAS. Mi-VII is due to a double mutation in glycophorin A converting an arginine
residue into a threonine residue and a tyrosine
residue into a serine at the positions 49 and 52 respectively. The threonine-49 residue is glycosylated. This appears to be the origin of one of the Mi-VII specific antigens (Anek) which is known to lie between residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). This also explains the loss of a high frequency antigen ((EnaKT)) found in normal glycophorin A which is located within the residues 46-56. Mi-VIII is due to a mutation at amino acid residue 49 (arginine
->threonine). M-VIII shares the Anek deteminant with MiVII. Mi-III, Mi-VI and Mi-X are due to rearrangements of glycophorin A and B in the order GlyA (alpha)-GlyB (delta)-GlyA (alpha). Mil-IX in contrast is a reverse alpha-delta-alpha hybrid gene. Mi-V, MiV(J.L.) and Sta are due to unequal but homologous crossing-over between alpha and delta glycophorin genes. The MiV and MiV(J.L.) genes are arranged in the same 5' alpha-delta 3' frame whereas Sta gene is in a reciprocal 5'delta-alpha 3' configuration.
Although uncommon in Caucasians (0.0098%) and Japan
ese (0.006%), the frequency of Mi-III is exceptionally high in several Taiwan
ese aboriginal tribes (up to 90%). In contrast its frequency is 2-3% in Han Taiwanese (Minnan). The Mi-III phenotype occurs in 6.28% of Hong Kong Chinese.
Mi-IX (MNS32) occurs with a frequency of 0.43% in Denmark
.
. Both the Dantu and the S-s-U- cells phenotypes have been shown to be protective against P. falciparum infection while the Henshaw phenotype is not protective.
Influenza A and B bind to glycophorin B.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the GYPB gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. GYPB has also recently been designated CD235b (cluster of differentiation
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
235b).
Function
Glycophorin AGYPA
Glycophorin A , also known as GYPA, is a protein which in humans is encoded by the GYPA gene. GYPA has also recently been designated CD235a .- Function :...
(GYPA) and B (GYPB; this protein) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinant
Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
s for the MN and Ss blood group
MNS antigen system
The MNS antigen system is a human blood group system based upon two genes on chromosome 4. There are currently 46 antigens in the system, but the five most important are called M, N, S, s, and U....
s respectively. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include the Miltenberger (Mi) complex and several isoforms of Stones (Sta); also Dantu, Sat, Henshaw (He or MNS6), Mg and deletion variants Ena, S-s-U- and Mk. Most of these are the result of gene recombinations between GYPA and GYPB.
Genomics
The gene is located on the long arm of chromosome 4 (4q28-q31) and has 5 exons. It was first sequenced in 1987 the peptide sequence of 72 amino acids having been determined earlier that year.The gene has 97% sequence homology with the glycophorin A gene from the 5' UTR approximately 1 kilobase upstream from the exon encoding the transmembrane regions to the portion of the coding sequence encoding the first 45 amino acids. There is a signal sequence of 19 amino acid residues. The leader peptide differs by one amino acid and the next 26 amino acids are identical. Amino acids 27-55 of glycophorin A are absent from glycophorin B. This section includes an N-glycosylation site. Only O-glycosylation sites are found on glycoprotein B and these are linked via serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
or threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
. Residues 80-100 of glycophorin A and 51-71 of glycophorin B are very similar. The intervening residues in contrast differ significantly. The antigenic determinant for the blood group Ss is located at residue 29 where S has a methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
and s a threonine. This is due to a mutation at nucleotide 143 (C->T). The S antigen is also known as MSN3 and the s antigen as MNS4.
It seems likely that this gene evolved by gene duplication and subsequent mutation of glycophorin A. The transition site from homologous to nonhomologous sequences can be localized within Alu repeat sequences.
Molecular biology
There are ~80000 copies of glycophorin B per erythrocyte. Both glycophorin A and B are expressed on the renal endothelium and epithelium.The first 40 amino acids of the mature protein are extracellular. The next 22 form a transmembrane segment and the remainder are intra cellular.
Blood groups
The MNS blood group was the second set of antigens discovered. M and N were identified in 1927 by Landsteiner and Levine. S and s in were described later in 1947The frequencies of these antigens are
- M: 78% CaucasianWhite peopleWhite people is a term which usually refers to human beings characterized, at least in part, by the light pigmentation of their skin...
; 74% Negroid - N: 72% Caucasian; 75% Negroid
- S: 55% Caucasian; 31% Negroid
- s: 89% Caucasian; 93% Negroid
Transfusion medicine
The M and N antigens differ at two amino acid residues: the M allele has serine at position 1 (C at nucleotide 2) and glycine at position 5 (G at nucleotide 14) while the N allele has leucine at position 1 (T at nucleotide 2) and glutamate at position 5 (A at nucleotide 14)Glycophorin B carries the blood group antigens N, Ss and U. Both glycophorin A and B bind the Vicia graminea anti-N lectin. S and s antigens are not affected by treatment with trypsin
Trypsin
Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...
or sialidase
Sialidase
Sialidases hydrolyse alpha--, alpha--, alpha--glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates...
but are destroyed or much depressed by treatment with papain
Papain
Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya .-Papain family:...
, pronase
Pronase
Pronase is a commercially available mixture of proteinases isolated from the extracellular fluid of Streptomyces griseus. Activity extends to both denatured and native proteins leading to complete or nearly complete digestion into individual amino acids....
or alpha-chymotrypsin.
There are about 40 known variants in the MNS blood group system. These have arisen largely as a result of mutations within the 4 kb region coding for the extracellular domain. These include the antigens Mv, Dantu, Henwshaw (He), Orriss (Or), Miltenberger, Raddon (FR) and Stones (Sta). Chimpanzee
Chimpanzee
Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...
s also have an MN blood antigen system. In chimpanzees M reacts strong but N only weakly.
Null mutants
Individuals who lack GypB have the phenotype S-s-U-. This may occur at frequencies of 20% in some African pygmies.In individuals who lack both glycophorin A and B the phenotype has been designated Mk.
Dantu antigen
The Dantu antigen was described in 1984. The Dantu antigen has an apparent molecular weight of 29 kiloDaltons (kDa) and 99 amino acids. The first 39 amino acids of the Dantu antigen are derived from glycophorin B and residues 40-99 are derived from glycophorin A. Dantu is associated with very weak s antigen, a protease resistant N antigen and either very weak or no U antigen. There are at least three variants: MD, NE and Ph. The Dantu phenotype occurs with a frequency of Dantu phenotype is ~0.005 in American Blacks and < 0.001 in Germans.Henshaw antigen
The Henshaw (He) antigen is due to a mutation of the N terminal region. There are three differences in the first three amino acid residues: the usual form has TryptophanTryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
1-Serine-Threonine-Serine-Glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
5 while Henshaw has Leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
1-Serine-Threonine-Threonine-Glutamate5. This antigen is rare in Caucasians but occurs at a frequency of 2.1% in US and UK of African origin. It occurs at the rate of 7.0% in blacks in Natal
Natal, South Africa
Natal is a region in South Africa. It stretches between the Indian Ocean in the south and east, the Drakensberg in the west, and the Lebombo Mountains in the north. The main cities are Pietermaritzburg and Durban...
and 2.7% in West Africans. At least 3 variants of this antigen have been identified.
Miltenberger subsystem
The Miltenberger (Mi) subsystem originally consisting of five phenotypes (Mia, Vw, Mur, Hil and Hut) now has 11 recognised phenotypes numbered I to XI (The antigen 'Mur' is named after to the patient the original serum was isolated from - a Mrs Murrel.) The name originally given to this complex refers to the reaction erythrocytes gave to the standard Miltenberger antisera used to test them. The subclasses were based on additional reactions with other standard antisera.Mi-I (Mia), Mi-II(Vw), Mi-VII and Mi-VIII are carried on glycophorin A. Mi-I is due to a mutation at amino acid 28 (threonine to methionine: C->T at nucleotide 83) resulting in a loss of the glycosylation at the asparagine26 residue. Mi-II is due to a mutation at amino acid 28 (threonine to lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
:C->A at nucleotide 83). Similar to the case of Mi-I this mutation results in a loss of the glycosylation at the asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
26 residue. This alteration in glycoslation is detectable by the presence of a new 32kDa glycoprotein stainable with PAS. Mi-VII is due to a double mutation in glycophorin A converting an arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
residue into a threonine residue and a tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
residue into a serine at the positions 49 and 52 respectively. The threonine-49 residue is glycosylated. This appears to be the origin of one of the Mi-VII specific antigens (Anek) which is known to lie between residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). This also explains the loss of a high frequency antigen ((EnaKT)) found in normal glycophorin A which is located within the residues 46-56. Mi-VIII is due to a mutation at amino acid residue 49 (arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
->threonine). M-VIII shares the Anek deteminant with MiVII. Mi-III, Mi-VI and Mi-X are due to rearrangements of glycophorin A and B in the order GlyA (alpha)-GlyB (delta)-GlyA (alpha). Mil-IX in contrast is a reverse alpha-delta-alpha hybrid gene. Mi-V, MiV(J.L.) and Sta are due to unequal but homologous crossing-over between alpha and delta glycophorin genes. The MiV and MiV(J.L.) genes are arranged in the same 5' alpha-delta 3' frame whereas Sta gene is in a reciprocal 5'delta-alpha 3' configuration.
Although uncommon in Caucasians (0.0098%) and Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
ese (0.006%), the frequency of Mi-III is exceptionally high in several Taiwan
Taiwan
Taiwan , also known, especially in the past, as Formosa , is the largest island of the same-named island group of East Asia in the western Pacific Ocean and located off the southeastern coast of mainland China. The island forms over 99% of the current territory of the Republic of China following...
ese aboriginal tribes (up to 90%). In contrast its frequency is 2-3% in Han Taiwanese (Minnan). The Mi-III phenotype occurs in 6.28% of Hong Kong Chinese.
Mi-IX (MNS32) occurs with a frequency of 0.43% in Denmark
Denmark
Denmark is a Scandinavian country in Northern Europe. The countries of Denmark and Greenland, as well as the Faroe Islands, constitute the Kingdom of Denmark . It is the southernmost of the Nordic countries, southwest of Sweden and south of Norway, and bordered to the south by Germany. Denmark...
.
Stone's antigen
Stones (Sta) has been shown to be the product of a hybrid gene of which the 5'-half is derived from the glycophorin B whereas the 3'-half is derived from the glycophorin A. Several isoforms are known. This antigen is now considered to be part of the Miltenberger complex.Sat antigen
A related antigen is Sat. This gene has six exons of which exon I to exon IV are identical to the N allele of glycophorin A whereas its 3' portion, including exon V and exon VI, are derived from the glycophorin B gene. The mature protein SAT protein contains 104 amino acid residues.Orissa antigen
Orriss (Or) appears to be a mutant of glyphorin A but its precise nature has not yet been determined.Transfusion reactions
Both anti-S and anti-s have been implicated in transfusion reactions and haemolytic disease of the newborn. Anti-M although occurring naturally has rarely been implicated in transfusion reactions. Anti-N is not considered to cause transfusion reactions. Severe reactions have been reported with anti-U and anti-Miltenberger. Anti Mi-I (Vw) and Mi-III has been recognised as a cause of hameolytic disease of the newborn. Raddon has been associated with severe transfusion reactions.Other areas
Glycophorin B acts as a receptor for erythrocyte binding protein 175 (EBA 175) of Plasmodium falciparumPlasmodium falciparum
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
. Both the Dantu and the S-s-U- cells phenotypes have been shown to be protective against P. falciparum infection while the Henshaw phenotype is not protective.
Influenza A and B bind to glycophorin B.